NC_000017.11:g.3600934_3658165del57232

NC_000017.11:g.3600934_3658165del57232

Variant type:
Deletion
Cytogenetic location:
17p13
Genomic location:
  • Chr17:3504228 - 3561459 (on Assembly GRCh37)
  • Chr17:3600934 - 3658165 (on Assembly GRCh38)
Other names:
  • 57-KB DEL
  • AF168787:g.36254_93510del
HGVS:
  • NC_000017.11:g.3600934_3658165del57232
  • NC_000017.10:g.3504228_3561459del57232
Links:
OMIM: 606272.0005

Clinical significance

NC_000017.11:g.3600934_3658165del57232

Clinical significance:
Pathogenic/Likely pathogenic
Review status:
(2/4)2 stars out of maximum of 4 stars
classified by multiple submitters
Number of submission(s):
4
Condition(s)
See supporting ClinVar records

1 Affected Gene

Recent Activity

Assertion and evidence details

Germline

Clinical significance
(Last evaluated)
Review status
(Assertion method)
Collection methodCondition(s)
(Mode of inheritance)
OriginCitationsSubmitter
(Last submitted)
Submission accession
Pathogenic
(Mar 19, 2010)
classified by single submitter
(literature only)
literature onlygermlinePubMed (9)
OMIM
(Dec 30, 2010)
SCV000024871
Pathogenic
(Mar 19, 2010)
classified by single submitter
(literature only)
literature onlygermlinePubMed (9)
OMIM
(Dec 30, 2010)
SCV000024872
Pathogenic
(Mar 19, 2010)
classified by single submitter
(literature only)
literature onlygermlinePubMed (9)
OMIM
(Dec 30, 2010)
SCV000024873
Pathogenic
(Aug 11, 2011)
classified by single submitter
(literature only)
literature onlynot providedPubMed (2)
GeneReviews
(Apr 30, 2013)
SCV000058483

Summary

FamiliesIndividualsSegregationAllele originEthnicityGeographic origin
not providednot providednot providedgermline, not providednot providednot provided

GeneReviews

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providednot provided

Description

not provided

OMIM

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providedgermline

Description

Bendavid et al. (2004) described a FISH method permitting cytogenetic laboratories to test for the 57-kb deletion, which is found in approximately 60% of patients with cystinosis in the United States and northern Europe.
Compound Heterozygosity for the 57-kb Deletion
Gahl et al. (2002) stated that the 57-kb deletion is found in the homozygous state in approximately 50% of patients of northern European descent who have cystinosis. This founder mutation, which removes the first 10 exons of CTNS and eliminates expression of the protein, apparently occurred in Germany in approximately 500 A.D. (Shotelersuk et al., 1998) and spread by migration to other regions, including Iceland.
In a 38-year-old woman who presented with photophobia at 38 years of age but had suffered chronic sensitivity to light (219750), Anikster et al. (2000) identified compound heterozygosity for the 57-kb deletion and a 928G-A transition, resulting in a glycine to arginine substitution at codon 197 (G197R; 606272.0011). Compound heterozygosity was also found in 2 additional patients from the same family with ocular cystinosis.
In a French/British report (Town et al., 1998), 23 (33%) of 70 patients with nephropathic cystinosis had a 65-kb deletion in the CTNS gene. Among American-based patients studied by Shotelersuk et al. (1998), 48 (44%) of 108 were homozygous for the 65-kb 'European' deletion. Of 96 alleles from these patients, 82 were assigned a nation of origin; 38 (46%) derived from Germany and 28 (34%) arose from the British Isles. Two apparently unrelated patients with homozygous deletions came from Iceland. In addition to the 48 patients homozygous for the 65-kb deletion, many of the patients may have a single copy of the deletion. An upstream deletion breakpoint needed to be determined before a PCR-based test of heterozygosity for the deletion could be developed.
In a Spanish patient with juvenile-onset nephropathic cystinosis (219900), Macias-Vidal et al. (2009) identified compound heterozygosity for a 416C-T transition in the CTNS gene, resulting in a ser139-to-phe (S139F; 606272.0018) substitution, and the 57-kb deletion.
This common mutation in nephropathic cystinosis (219800) was originally reported as a 65-kb deletion. Touchman et al. (2000) sequenced 200 kb surrounding the CTNS gene and found that the deletion is approximately 57 rather than 65 kb. The authors identified SHPK (605060), which they designated CARKL, within this deleted region. The findings indicated that the 57-kb deletion includes deletion of CARKL in addition to CTNS, which may account for phenotypic variability in patients.
Wamelink et al. (2008) found that cystinosis patients homozygous for the 57-kb deletion had increased urinary sedoheptulose and erythritol compared to patients with other CTNS mutations. Enzyme studies of cultured fibroblasts revealed an 80% reduction in sedoheptulose phosphorylating activity compared to cystinosis patients with other mutations and controls. The findings indicated that the CARKL gene encodes sedoheptulokinase, which functions in the pentose phosphate pathway.

Last Updated: Jun 28, 2014

Write to the Help Desk